The major focus of this program is on disease site-specific therapy. Locally advanced prostate cancer and bladder cancer are deep-seated tumor sites with high rates of local failure. In order to improve the local tumor control in these sites we will take advantage of the syergistic effect between hyperthermia (HT) and radiation. Using a site-specific approach to heat the prostate and the bladder we will test the hypothesis that the combination of heat and irradiation leads to improved local tumor control which may lead to increased patient survival. We plan to correlate clinical outcome with the tumor and normal tissue temperatures achieved and with biological parameters measured in biopsy sampler of patient's tumors. The three specific areas of clinical research are as follows; PROSTATE CANCER: We are combining a site-specific HT treatment method with radiation therapy (RT) to treat patients with locally advanced adenocarcinoma of the prostate. HT will be delivered twice during standard RT using a previously developed transrectal ultrasound applicator that has been shown capable of heating the prostate gland. The primary endpoints for this Phase II study are toxicity and efficacy (as measured by tumor response). Survival and quality of life will also be evaluated. DEEP TUMORS: We will continue to evaluate athe capabilities and limitations of athe focused segmented ultrasound machine (FSUM) hyperthermia system combined with radiation therapy to treat advanced and deep seated tumors using the clinical protocol in progress. We also plan to evaluate athe potential role of RT delivered by the FSUM when combined with external beam RT to treat patients with medically inoperable or advanced transitional cell carcinoma of the bladder. HT will be delivered twice during the course of RT; warn irrigation of the bladder is available to improve the homogeneity of HT. Improved local tumor control in these patients may lead to more frequent urinary bladder organ preservation. HYPERTHERMIA MODIFIERS: We will determine the efficacy and toxicity of combined HT, RT, and chemical modifiers in a series of Phase II clinical trials designed to treat locally persistent, recurrent, or metastic superficial tumors. The first modifier to be tested will be etanidazole; the second study will evaluate tirapazimine.